Phosphatidylserines

Draw the structures of (a) all the possible triacylglycerols that can be formed from glycerol with stearic and arachidonic acid, and (b) all the phosphatidylserine isomers that can be formed from palmitic and linolenic acids. 

Lipids in model systems are often found in asymmetric clusters (see Figure 9.8). Such behavior is referred to as a phase separation, which arises either spontaneously or as the result of some extraneous influence. Phase separations can be induced in model membranes by divalent cations, which interact with negatively charged moieties on the surface of the bilayer. For example, Ca induces phase separations in membranes formed from phosphatidylserine (PS)... 

FIGURE 9.8 An illustration of the concept of lateral phase separations in a membrane. Phase separations of phosphatidylserine (green circles) can be indnced by divalent cations snch as Ca-+. 

Discuss the effects on the lipid phase transition of pure dimyris-toyl phosphatidylcholine vesicles of added (a) divalent cations, (b) cholesterol, (c) distearoyl phosphatidylserine, (d) dioleoyl phosphatidylcholine, and (e) integral membrane proteins. 

Exchange of Ethanolamine for Serine Converts Phosphatidylethanolamine to Phosphatidylserine... 

Mammals synthesize phosphatidylserine (PS) in a calcium ion-dependent reaction involving aminoalcohol exchange (Figure 25.21). The enzyme catalyzing this reaction is associated with the endoplasmic reticulum and will accept phosphatidylethanolamine (PE) and other phospholipid substrates. A mitochondrial PS decarboxylase can subsequently convert PS to PE. No other pathway converting serine to ethanolamine has been found. 

Phosphatidic acid Phosphatidylcholine Phosphatidyl- ethanolamine Phosphatidylserine... 

One of the early events of the apoptotic process involves the translocation of phosphatidylserine on the surface of cell membranes annexin V binding and propidium iodide uptake reveals various cellular states. After treatment with organotin(IV) compounds the cells could be categorized into populations vital cells (annexin V /P ), early apoptotic cells (annexin V /P ), late apoptotic cells (annexin V /P ), and necrotic cells (annexin V /P" ). Cells are observed with a fluorescence microscope and it is possible to observe translocation of phosphatidylserine (PS) from the inner side of the plasma membrane to the outer one and to see a green stain for annexin V FLUOS bound to PS, and a red stain for propidium iodide. 

MacDonald, R.C., Simon, S.P. Baer, E. (1976). Ionic influences on the phase transitions of dipalmitoyl phosphatidylserine. Biochemistry, 15, 885-97. 

FIGURE 1 Effect of (sequential) extrusion of MLV dispersions through polycarbonate membrane filters (Unipore) with pore sizes of 1.0, 0.6, 0.4, 0.2, and 0.1 ym on the mean liposome diameter. DXR-containing MLV (phosphatidylcholine/phosphatidylserine/ cholesterol 10 1 4) mean diameter of nonextruded dispersion about 2 ym pH 4. Mean particle size determined by dynamic Light scattering (Nanosizer, Coulter Electronics). (From Crommelin and Storm, 1987.)... 

Pharmacological effects of phosphatidylserine liposomes The role of lysophosphatidylserine, Br. J. Pharmacol.. 67. 611-616. 

Maneta-Peyret, L., Bessoule, J. J., Geffard, M., and Cassagne, C. (1988). Demonstration of high specificity antibodies against phosphatidylserine, J. Immunol. Meth.. 108, 123-127. 

There is also inside-outside (transverse) asymmetry of the phospholipids. The choline-containing phospholipids (phosphatidylcholine and sphingomyelin) are located mainly in the outer molecular layer the aminophospholipids (phosphatidylserine and phos-phatidylethanolamine) are preferentially located in the inner leaflet. Obviously, if this asymmetry is to exist at all, there must be limited transverse mobility (flip-flop) of the membrane phospholipids. In fact, phospholipids in synthetic bilayers exhibit an extraordinarily slow rate of flip-flop the half-life of the asymmetry can be measured in several weeks. However, when certain membrane proteins such as the erythrocyte protein gly-cophorin are inserted artificially into synthetic bilayers, the frequency of phospholipid flip-flop may increase as much as 100-fold. 

The major lipid classes are phospholipids and cholesterol the major phospholipids are phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylserine (PS) along with sphingomyelin (Sph). 

We have proposed that vesicle aggregation is probably related to the disposition of pardaxin bound in the phosphatidylserine vesicle lipid bilayer (26). This conclusion is supported by the observation that phosphatidycholine vesicles are not induced to aggregate and that the pardaxin-induced phosphatidylserine vesicle aggregation is affected by charge polarization of the vesicle (26). This suggestion seems to be consistent also with the voltage dependence of fast "pore" activity of pardaxin, the channels which are open only at positive membrane potentials. 

Most probably the presence of pardaxin pores alters the structure of the bilayer resulting in aggregation of phosphatidylserine vesicles mediated by contact but not by partial merging of their membranes. 

Phosphatidylcholine, commonly known as lecithin, is the most commonly occurring in natnre and consists of two fatty add moieties in each molecule. Phosphati-dylethanolamine, also known as cephahn, consists of an amine gronp that can be methylated to form other compounds. This is also one of the abundant phospholipids of animal, plant, and microbial origin. Phosphatidylserine, which has weakly acidic properties and is found in the brain tissues of mammals, is found in small amounts in microorganisms. Recent health claims indicate that phosphatidylserine can be used as a brain food for early Alzheimer s disease patients and for patients with cognitive dysfunctions. Lysophospholipids consist of only one fatty acid moiety attached either to sn-1 or sn-2 position in each molecule, and some of them are quite soluble in water. Lysophosphatidylchohne, lysophosphatidylserine, and lysophos-phatidylethanolamine are found in animal tissues in trace amounts, and they are mainly hydrolytic products of phospholipids. 

FIGURE 12.4 (A) Diagrammatic representation of the separation of major simple lipid classes on silica gel TLC — solvent system hexane diethylether formic acid (80 20 2) (CE = cholesteryl esters, WE = wax esters, HC = hydrocarbon, EEA = free fatty acids, TG = triacylglycerol, CHO = cholesterol, DG = diacylglycerol, PL = phospholipids and other complex lipids). (B) Diagrammatic representation of the separation of major phospholipids on silica gel TLC — solvent sytem chloroform methanol water (70 30 3) (PA = phosphatidic acid, PE = phosphatidylethanolamine, PS = phosphatidylserine, PC = phosphatidylcholine, SPM = sphingomyelin, LPC = Lysophosphatidylcholine). 

PPD Purified protein derivative PPME Polymeric polysaccharide rich in mannose-6-phosphate moieties PRA Percentage reactive activity PRD, PRDII Positive regulatory domain, -II PR3 Proteinase-3 PRBC Parasitized red blood cell proET-1 Proendothelin-1 PRL Prolactin PRP Platelet-rich plasma PS Phosphatidylserine P-selectin Platelet selectin formerly known as platelet adctivation-dependent granule external membrane protein (PADGEM), granule membrane protein of MW 140 kD (GMP-140)... 

---